Decoding the Lipidome of Adipose-Derived Extracellular Vesicles in Ovarian Cancer: Mechanistic Insight into Tumor-Adipose Crosstalk

Objective

Ovarian cancer (OC) is among the most lethal gynaecological malignancies, with a distinct tendency to metastasize to the omentum, an adipose tissue depot that provides both a physical scaffold and a metabolic reservoir for tumour cells. In this metastatic niche, adipocytes undergo a phenotypic transformation into cancer-associated adipocytes (CAAs), characterized by enhanced lipid mobilization and inflammatory signalling, further contributing to tumour progression. At advanced stages, the tumour microenvironment (TME) is further remodelled by the accumulation of malignant ascites, a fluid enriched in soluble mediators and extracellular vesicles (EVs), which are pivotal mediators of intercellular communication within the TME. While their protein and nucleic acid cargo has been extensively characterized, the lipid composition of adipose tissue-derived EVs and its contribution to OC progression remain poorly understood. The Lipid-Ex project aims to address this gap by investigating how bioactive lipids within EVs influence tumour behaviour through three objectives: (1) characterizing the lipidomic profile of adipose tissue–derived EVs in OC, (2) investigating the functional effects of lipid-containing EVs on recipient tumour cells, and (3) dissecting the lipid-mediated signalling between adipose tissue and OC cells. Lipid-Ex hypothesizes that EVs from adipose tissue carry bioactive lipids that engage specific receptors on OC cells, enhancing intercellular communication and promoting tumour progression and metastasis. Furthermore, Lipid-Ex anticipate that cancer associated adipose tissue (CAAT)-derived EVs possess a distinct lipid signature that fosters a more aggressive TME. By providing the first comprehensive characterization of lipid species in adipose tissue–derived EVs and defining their functional impact, Lipid-Ex seeks to fulfil this gap in the tumour-adipose crosstalk.